N-phenyl-N'-pyridinylureas as anticonvulsant agents.
A series of N-phenyl-N'-pyridinylureas was examined for anticonvulsant activity. Extensive structure/activity investigations revealed optimal activity in the N-(2,6-disubstituted-phenyl)-N'-(4-pyridinyl)urea series, with 37 exhibiting the best overall anticonvulsant profile. Compound 37 was effective against seizures induced by maximal electroshock but did not protect mice from clonic seizures produced by the convulsant pentylenetetrazol. The overall pharmacological profile suggests that 37 would be of therapeutic use in the treatment of generalized tonic-clonic and partial seizures. Compound 37 was selected for Phase 1 clinical trials.
Pavia
M R
MR
Department of Chemistry, Warner-Lambert Company, Ann Arbor, Michigan 48105.
Lobbestael
S J
SJ
Taylor
C P
CP
Hershenson
F M
FM
Miskell
D L
DL
D000284:Administration, Oral; D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis*; D001259:Ataxia / Q000139:chemically induced; D055598:Chemical Phenomena; D002621:Chemistry; D004305:Dose-Response Relationship, Drug; D051379:Mice; D010671:Phenylurea Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000927:Anticonvulsants; D010671:Phenylurea Compounds; C062824:N-(2-chloro-6-methylphenyl)-N'-(4-pyridinyl)urea